Characterizing Natural Recovery of People With Initial Motor Complete Tetraplegia.

OBJECTIVE: To determine the differences in neurologic recovery in persons with initial cervical American Spinal Cord Injury Association Impairment Scale (AIS) grades A and B over time. DESIGN: Retrospective analysis of data from people with traumatic cervical spinal cord injury (SCI) enrolled in the National Spinal Cord Injury Model Systems (SCIMS) database from 2011-2019. SETTING: SCIMS centers. PARTICIPANTS: Individuals (N=187) with traumatic cervical (C1-C7 motor level) SCI admitted with initial AIS grade A and B injuries within 30 days of injury, age 16 years or older, upper extremity motor score (UEMS) ≤20 on both sides, and complete neurologic data at admission and follow-up between 6 months and 2 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Conversion in AIS grades, UEMS and lower extremity motor scores (LEMS), and sensory scores. RESULTS: Mean time to initial and follow-up examinations were 16.1±7.3 days and 377.5±93.4 days, respectively. Conversion from an initial cervical AIS grades A and B to motor incomplete status was 13.4% and 50.0%, respectively. The mean UEMS change for people with initial AIS grades A and B did not differ (7.8±6.5 and 8.8±6.1; P=.307), but people with AIS grade B experienced significantly higher means of LEMS change (2.3±7.4 and 8.8±13.9 (P≤.001). The increased rate of conversion to motor incomplete status from initial AIS grade B appears to be the primary driving factor of increased overall motor recovery. Individuals with initial AIS grade B had greater improvement in sensory scores. CONCLUSIONS: While UEMS recovery is similar in persons with initial AIS grades A and B, the rate of conversion to motor incomplete status, LEMS, and sensory recovery are significantly different. This information is important for clinical as well as research considerations.

Long-Term Follow-Up of Patients With Ventilator-Dependent High Tetraplegia Managed With Diaphragmatic Pacing Systems.

OBJECTIVE: To explore participants' experiences after implantation of a diaphragmatic pacing system (DPS). DESIGN: Cross-sectional, observational study using self-report questionnaires. SETTING: Participants were recruited from 6 Spinal Cord Injury Model System centers across the United States (Craig Hospital, CO; Jefferson/Magee Rehabilitation Hospital, PA; Kessler Rehabilitation Center, NJ; University of Miami, FL; The Shirly Ryan Ability Lab, IL; Shepherd Center, GA). INTERVENTIONS: Not applicable. PARTICIPANTS: Men and women (N=28) with tetraplegia were enrolled in the study between November 2012 and January 2015. MAIN OUTCOME MEASURES: Participants completed self-report questionnaires focused on their DPS usage and mechanical ventilation, as well as their experiences and satisfaction with the DPS. RESULTS: DPS is a well-tolerated and highly successful device to help individuals living with spinal cord injury who are dependent on ventilators achieve negative pressure, ventilator-free breathing. A small percentage of participants reported complications, including broken pacing wires and surgery to replace or reposition wires. CONCLUSIONS: This study provides insight into the usage patterns of DPS and both the potential negative and positive effects that DPS can have on the life of the user. Knowledge gained from this study can provide a foundation for further discussion about the benefits and potential risks of using a DPS to inform an individual's decision to pursue a DPS implant.

Characterizing the Experience of Spasticity after Spinal Cord Injury: A National Survey Project of the Spinal Cord Injury Model Systems Centers.

OBJECTIVE: To characterize the qualities that individuals with spinal cord injury (SCI) associate with their experience of spasticity and to describe the relationship between spasticity and perceived quality of life and the perceived value of spasticity management approaches. DESIGN: Online cross-sectional survey. SETTING: Multicenter collaboration among 6 Spinal Cord Injury Model Systems hospitals in the United States. PARTICIPANTS: Individuals with SCI (N=1076). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Qualities of Spasticity Questionnaire, modified Spinal Cord Injury-Spasticity Evaluation Tool (mSCI-SET), and the modified Patient-Reported Impact of Spasticity Measure (mPRISM). RESULTS: Respondents indicated that spasms most often occurred in response to movement-related triggering events. However, spontaneous spasms (ie, no triggering event) were also reported to be among the most common types. Frequency of spasms appears to decline with age. The highest frequency of spasms was reported by 56% of respondents aged <25 years and by only 28% of those >55 years. Stiffness associated with spasticity was reported to be more common than spasms (legs, 65% vs 54%; trunk, 33% vs 18%; arms, 26% vs 15%). Respondents reported negative effects of spasticity more commonly than positive effects. Based on their association with negative scores on the mSCI-SET and the mPRISM, the 5 most problematic experiences reported were stiffness all day, interference with sleep, painful spasms, perceived link between spasticity and pain, and intensification of pain before a spasm. Respondents indicated spasticity was improved more by stretching (48%) and exercise (45%) than by antispasmodics (38%). CONCLUSIONS: The experience of spasticity after SCI is complex and multidimensional, with consequences that affect mobility, sleep, comfort, and quality of life. Stiffness, rather than spasms, appears to be the most problematic characteristic of spasticity. Physical therapeutic interventions to treat spasticity warrant in-depth investigation.

Developing guiding principles for technology-based rehabilitation program by engaging people with motor incomplete tetraplegia.

BACKGROUND: Technology-aided rehabilitation is well established in the field of neurologic rehabilitation. Despite the widespread availability, the development of technology-based interventions that incorporate perspectives of the people who will use them is lacking. OBJECTIVES: This qualitative study aims to understand how people with chronic motor incomplete cervical spinal cord injury view rehabilitation technology to improve upper extremity function and neuromuscular recovery to inform future intervention development. METHODS: Seven participants with chronic upper extremity impairment due to spinal cord injury/dysfunction trialed five rehabilitation technology devices. After a 30-45 min trial for each device, participants engaged in a semi-structured interview. Interviews were analyzed using a qualitative approach to explore the experience using and understand features that support motivation to use of rehabilitation technology. RESULTS: Qualitative analysis revealed three major themes: (1) devices must be flexible to meet diverse needs; (2) intervention protocols must be individualized to address unique needs and contexts of users; (3) intervention protocols should be developed and updated by a skilled clinician. These themes and subthemes were used to describe guiding principles to inform future intervention design. CONCLUSION: The experiences of people with cervical spinal cord injury can be elicited as part of the intervention design process to systematically develop protocols for future feasibility trials. The findings from this study can be used to inform the development of technology-aided rehabilitation programs to improve upper extremity function in people with chronic motor incomplete tetraplegia. CLINICAL TRIALS REGISTRATION NUMBER: NCT04000256.

A Comparison of Diagnostic Stability of the ASIA Impairment Scale Versus Frankel Classification Systems for Traumatic Spinal Cord Injury.

OBJECTIVE: To determine whether the "sacral sparing" definition for completeness of traumatic spinal cord injury (SCI) is a more stable definition than the previously used Frankel Classification. DESIGN: Retrospective analysis of individuals enrolled in the Spinal Cord Injury Model Systems (SCIMS) database between 2011 and 2018. SETTING: SCIMS centers. PARTICIPANTS: Individuals (N=804) with traumatic SCI who were at least 16 years old at time of injury, were admitted to rehabilitation within 30 days, had American Spinal Injury Association Impairment Scale (AIS) grades A-D at admission, and had complete neurologic data at the time of admission and 1 year. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Frankel and AIS scores were computed for a cohort of 804 eligible cases. Stability was compared between the 2 classification systems by calculating the proportions of cases in which regression (conversion to a more severe impairment level) was observed. RESULTS: A larger proportion of individuals classified with "incomplete" injuries (grades B-D) at the time of admission using the Frankel system regressed to complete status at 1 year compared with the AIS criteria (9.4% vs 2.0%). Those with grade B injuries regressed to grade A more often using the Frankel system compared with the AIS system (19.7% to 5.4%). A larger proportion of people diagnosed as Frankel grade C or D regressed to Frankel grade A compared with individuals diagnosed as AIS grade C or D who regressed to AIS grade A (5.0% to 1.1%). CONCLUSIONS: More individuals diagnosed with neurologically incomplete SCI regressed to complete status at 1 year when using the Frankel system compared with AIS classification, which is based on sacral sparing. This reinforces the finding that the "sacral sparing" definition is a more stable classification in traumatic SCI.

The effect of zoledronic acid on attenuation of bone loss at the hip and knee following acute traumatic spinal cord injury: a randomized-controlled study.

STUDY DESIGN: Randomized double blind, placebo-controlled trial. OBJECTIVES: To examine the effect of early intravenous zoledronic acid (ZA) on bone markers and areal bone mineral density (aBMD) in persons with acute ASIA Impairment Scale (AIS) A traumatic spinal cord injury (SCI). SETTING: Two inpatient rehabilitation units. METHODS: Thirteen men, 2 women, aged 19-65, C4-T10 AIS A SCI, received 5 mg intravenous ZA vs. placebo 12-21 days post injury. Markers of bone formation (procollagen N-1 terminal propeptide [P1NP]), bone resorption (serum C-telopeptide [CTX]), and aBMD by dual-energy X-ray absorptiometry (DXA) for hip (femur-proximal, intertrochanteric, neck), and knee (distal femur, proximal tibia) were obtained at baseline, 2 weeks post infusion (P1NP, CTX only), 4 and 12 months post injury. RESULTS: P1NP remained unchanged, while CTX decreased in ZA but increased in controls at 2 weeks (mean difference = -97%, p < 0.01), 4 months (mean difference = -54%, p < 0.05), but not 12 months (mean difference = 3%, p = 0.23). Changes in aBMD at the hip favored ZA at 4 months (mean difference 10.3-14.1%, p < 0.01) and 12 months (mean difference 10.8-13.1%, p < 0.02). At 4 months, changes in aBMD favored ZA at the distal femur (mean difference 6.0%, 95% CI: 0.7-11.2, p < 0.03) but not proximal tibia (mean difference 8.3%, 95% CI: -6.9 to 23.6, p < 0.23). Both groups declined in aBMD at 12 months, with no between group differences. CONCLUSION: ZA administered ≤21 days of complete traumatic SCI maintains aBMD at the hip and distal femur at 4 months post injury. This effect is partially maintained at 12 months.

Sensitivity of the SCI-FI/AT in Individuals With Traumatic Spinal Cord Injury.

OBJECTIVE: To examine the ability of the Spinal Cord Injury-Functional Index/Assistive Technology (SCI-FI/AT) measure to detect change in persons with spinal cord injury (SCI). DESIGN: Multisite longitudinal (12-mo follow-up) study. SETTING: Nine SCI Model Systems programs. PARTICIPANTS: Adults (N=165) with SCI enrolled in the SCI Model Systems database. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: SCI-FI/AT computerized adaptive test (CAT) (Basic Mobility, Self-Care, Fine Motor Function, Wheelchair Mobility, and/or Ambulation domains) completed at discharge from rehabilitation and 12 months after SCI. For each domain, effect size estimates and 95% confidence intervals were calculated for subgroups with paraplegia and tetraplegia. RESULTS: The demographic characteristics of the sample were as follows: 46% (n=76) individuals with paraplegia, 76% (n=125) male participants, 57% (n=94) used a manual wheelchair, 38% (n=63) used a power wheelchair, 30% (n=50) were ambulatory. For individuals with paraplegia, the Basic Mobility, Self-Care, and Ambulation domains of the SCI-FI/AT detected a significantly large amount of change; in contrast, the Fine Motor Function and Wheelchair Mobility domains detected only a small amount of change. For those with tetraplegia, the Basic Mobility, Fine Motor Function, and Self-Care domains detected a small amount of change whereas the Ambulation item domain detected a medium amount of change. The Wheelchair Mobility domain for people with tetraplegia was the only SCI-FI/AT domain that did not detect significant change. CONCLUSIONS: SCI-FI/AT CAT item banks detected an increase in function from discharge to 12 months after SCI. The effect size estimates for the SCI-FI/AT CAT vary by domain and level of lesion. Findings support the use of the SCI-FI/AT CAT in the population with SCI and highlight the importance of multidimensional functional measures.

Considerations and recommendations for selection and utilization of upper extremity clinical outcome assessments in human spinal cord injury trials.

STUDY DESIGN: This is a focused review article. OBJECTIVES: This review presents important features of clinical outcomes assessments (COAs) in human spinal cord injury research. Considerations for COAs by trial phase and International Classification of Functioning, Disability and Health are presented as well as strengths and recommendations for upper extremity COAs for research. Clinical trial tools and designs to address recruitment challenges are identified. METHODS: The methods include a summary of topics discussed during a two-day workshop, conceptual discussion of upper extremity COAs and additional focused literature review. RESULTS: COAs must be appropriate to trial phase and particularly in mid-late-phase trials, should reflect recovery vs. compensation, as well as being clinically meaningful. The impact and extent of upper vs. lower motoneuron disease should be considered, as this may affect how an individual may respond to a given therapeutic. For trials with broad inclusion criteria, the content of COAs should cover all severities and levels of SCI. Specific measures to assess upper extremity function as well as more comprehensive COAs are under development. In addition to appropriate use of COAs, methods to increase recruitment, such as adaptive trial designs and prognostic modeling to prospectively stratify heterogeneous populations into appropriate cohorts should be considered. CONCLUSIONS: With an increasing number of clinical trials focusing on improving upper extremity function, it is essential to consider a range of factors when choosing a COA. SPONSORS: Craig H. Neilsen Foundation, Spinal Cord Outcomes Partnership Endeavor.

Influence of Age Alone, and Age Combined With Pinprick, on Recovery of Walking Function in Motor Complete, Sensory Incomplete Spinal Cord Injury.

OBJECTIVE: To determine if age, pinprick scores in the lower extremities, and neurologic severity of injury influence recovery of ambulation in persons with motor complete, sensory incomplete (American Spinal Injury Association Impairment Scale [AIS] grade B) spinal cord injury (SCI) 1 year after initial injury. DESIGN: This retrospective analysis examined subjects with AIS grade B from the Spinal Cord Injury Model System (SCIMS) database from 2006 to 2015. The baseline neurologic examination at rehabilitation admission (2-4wk postinjury) was used for comparison with 1-year outcome measures of locomotion. SETTING: Fifteen acute inpatient rehabilitation centers (participants in the SCIMS database). PARTICIPANTS: Participants with AIS grade B SCI (N=249) were enrolled in the SCIMS database in 2 cycles (2006-2010 and 2011-2015). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Household ambulation at 1 year by FONE-FIM and by direct interview, as part of the annual neurologic exam; change in American Spinal Injury Association score 1 year postinjury. RESULTS: Findings demonstrate a statistically nonsignificant increase in likelihood of walking for those age <50 years compared with those age ≥50 years (relative risk [RR]=1.99; 95% confidence interval, 0.80-3.04). Presence of pinprick in at least one half of the lower-extremity dermatomes L2-S1 was associated with higher likelihood of walking (RR=5.57, P=.0023). Pinprick was significant for patients age <50 years (RR=4.58, P=.0090) but not for those age ≥50 years (P=.15). CONCLUSIONS: Compared with younger individuals, participants age ≥50 years with AIS grade B SCI are less likely to achieve walking function 1 year postinjury. Likewise, preservation of pinprick sensation postinjury in the majority of lower-extremity dermatomes L2-S1 increases the chances of walking in individuals age <50 years.

Patterns of Sacral Sparing Components on Neurologic Recovery in Newly Injured Persons With Traumatic Spinal Cord Injury.

OBJECTIVE: To assess the patterns of sacral sparing and recovery in newly injured persons with traumatic spinal cord injury (SCI). DESIGN: Retrospective analysis of data from the national Spinal Cord Injury Model Systems (SCIMS) database for patients enrolled from January 2011 to February 2015. SETTING: SCIMS centers. PARTICIPANTS: Individuals (N=1738; age ≥16y) with traumatic SCI admitted to rehabilitation within 30 days after injury with follow-up at discharge, at 1 year, or both. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: International Standards for Neurological Classification of Spinal Cord Injury examination results at admission and follow-up (discharge or 1y, or both). RESULTS: Conversion from an initial American Spinal Injury Association Impairment Scale (AIS) grade A to incomplete status was 20% at rehabilitation discharge and 27.8% at 1 year, and was greater in cervical and low paraplegia levels (T10 and below) than in high paraplegia level injuries (T1-9). Conversion from AIS B to motor incomplete was 33.9% at discharge and 53.6% at 1 year, and the initial sparing of all sacral sensory components was correlated with the greatest conversion to motor incomplete status at discharge and at 1 year. For patients with initial AIS C, the presence of voluntary anal contraction (VAC) in association with other sacral sparing was most frequently observed to improve to AIS D status at discharge. However, the presence of VAC alone as the initial sacral sparing component had the poorest prognosis for recovery to AIS D status. At follow-up, regaining sacral sparing components correlated with improvement in conversion for patients with initial AIS B and C. CONCLUSIONS: The components of initial and follow-up sacral sparing indicated differential patterns of neurologic outcome in persons with traumatic SCI. The more sacral components initially spared, the greater the potential for recovery; and the more sacral components gained, the greater the chance of motor recovery. Consideration of whether VAC should remain a diagnostic criterion sufficient for motor incomplete classification in the absence of other qualifying sublesional motor sparing is recommended.

Reliability and Validity of S3 Pressure Sensation as an Alternative to Deep Anal Pressure in Neurologic Classification of Persons With Spinal Cord Injury.

OBJECTIVE: To determine whether pressure sensation at the S3 dermatome (a new test) could be used in place of deep anal pressure (DAP) to determine completeness of injury as part of the International Standards for Neurological Classification of Spinal Cord Injury. DESIGN: Prospective, multicenter observational study. SETTING: U.S. Spinal Cord Injury Model Systems. PARTICIPANTS: Persons (N=125) with acute traumatic spinal cord injury (SCI), neurologic levels T12 and above, were serially examined at 1 month (baseline), 3, 6, and 12 months postinjury. There were 80 subjects with tetraplegia and 45 with paraplegia. INTERVENTIONS: S3 pressure sensation at all time points, with a retest at the 1-month time point. MAIN OUTCOME MEASURES: Test-retest reliability and agreement (κ), sensitivity, specificity, positive and negative predictive values. RESULTS: Test-retest reliability of S3 pressure at 1 month was almost perfect (κ=.98). Agreement of S3 pressure with DAP was substantial both at 1 month (κ=.73) and for all time points combined (κ=.76). The positive predictive value of S3 pressure for DAP was 89.3% at baseline and 90.3% for all time points. No pattern in outcomes was seen in those cases where S3 pressure and DAP differed at 1 month. CONCLUSIONS: S3 pressure sensation is reliable and has substantial agreement with DAP in persons with SCI at least 1 month postinjury. We suggest S3 pressure as an alternative test of sensory sacral sparing for supraconus SCI, at least in cases where DAP cannot be tested. Further research is needed to determine whether S3 pressure could replace DAP for classification of SCI.

Musculoskeletal Effects of 2 Functional Electrical Stimulation Cycling Paradigms Conducted at Different Cadences for People With Spinal Cord Injury: A Pilot Study.

OBJECTIVE: To compare the musculoskeletal effects of low cadence cycling with functional electrical stimulation (FES) with high cadence FES cycling for people with spinal cord injury (SCI). DESIGN: Randomized pre-post design. SETTING: Outpatient rehabilitation clinic. PARTICIPANTS: Participants (N=17; 14 men, 3 women; age range, 22-67y) with C4-T6 motor complete chronic SCI were randomized to low cadence cycling (n=9) or high cadence cycling (n=8). INTERVENTIONS: Low cadence cycling at 20 revolutions per minute (RPM) and high cadence cycling at 50 RPM 3 times per week for 6 months. Cycling torque (resistance per pedal rotation) increased if targeted cycling cadence was maintained. MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry was used to assess distal femur areal bone mineral density, magnetic resonance imaging was used to assess to assess trabecular bone microarchitecture and cortical bone macroarchitecture and thigh muscle volume, and biochemical markers were used to assess bone turnover. It was hypothesized that subjects using low cadence cycling would cycle with greater torque and therefore show greater musculoskeletal improvements than subjects using high cadence cycling. RESULTS: A total of 15 participants completed the study. Low cadence cycling obtained a maximal average torque of 2.9±2.8Nm, and high cadence cycling obtained a maximal average torque of 0.8±0.2Nm. Low cadence cycling showed greater decreases in bone-specific alkaline phosphatase, indicating less bone formation (15.5% decrease for low cadence cycling, 10.7% increase for high cadence cycling). N-telopeptide decreased 34% following low cadence cycling, indicating decreased resorption. Both groups increased muscle volume (low cadence cycling by 19%, high cadence cycling by 10%). Low cadence cycling resulted in a nonsignificant 7% increase in apparent trabecular number (P=.08) and 6% decrease in apparent trabecular separation (P=.08) in the distal femur, whereas high cadence cycling resulted in a nonsignificant (P>.3) 2% decrease and 3% increase, respectively. CONCLUSIONS: This study suggests that the greater torque achieved with low cadence cycling may result in improved bone health because of decreased bone turnover and improved trabecular bone microarchitecture. Longer-term outcome studies are warranted to identify the effect on fracture risk.

Spinal Cord Injury-Functional Index/Assistive Technology Short Forms.

OBJECTIVES: To evaluate the psychometric properties of the Spinal Cord Injury-Functional Index/Assistive Technology (SCI-FI/AT) short forms (SFs) in the domains of basic mobility, self-care, fine motor function, and ambulation based on internal consistency; correlations between SFs and full item banks, and a 10-item computerized adaptive test (CAT) version; magnitude of ceiling and floor effects; and measurement precision across a broad range of function in a sample of adults with spinal cord injury (SCI). DESIGN: Cross-sectional cohort study. SETTING: Nine national Spinal Cord Injury Model Systems programs. PARTICIPANTS: A sample of adults with traumatic SCI (N=460) stratified by level of injury (paraplegia/tetraplegia), completeness of injury, and time since SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: SCI-FI/AT full item bank, 10-item CAT, and SFs (with separate Self-Care and Fine Motor Function SFs for persons with tetraplegia and paraplegia). RESULTS: The SCI-FI/AT SFs demonstrated very good internal consistency, group-level reliability, and excellent correlations between SFs and scores based on the CAT version and the total item bank. Ceiling and floor effects are acceptable (except for unacceptable ceiling effects for persons with paraplegia on the Self-Care and Fine Motor Function SFs). The test information functions are excellent across a broad range of functioning typical of persons with paraplegia and tetraplegia. CONCLUSIONS: Clinicians and researchers should consider using the SCI-FI/AT SFs to assess functioning with the use of assistive technology when CAT applications are not available.

Can anatomic level of injury on MRI predict neurological level in acute cervical spinal cord injury?

BACKGROUND: Determining neurological level of injury (NLI) is of paramount importance after spinal cord injury (SCI), although its accuracy depends upon the reliability of the neurologic examination. Here, we determine if anatomic location of cervical cord injury by MRI (MRI level of injury) can predict NLI in the acute traumatic setting. METHODS: A retrospective review was undertaken of SCI patients with macroscopic evidence of cervical cord injury from non-penetrating trauma, all of whom had undergone cervical spine MRI and complete neurologic testing. The recorded MRI information included cord lesion type (intra-axial edema, hemorrhage) and MRI locations of upper and lower lesion boundary, as well as lesion epicenter. Pearson correlation and Bland-Altman analyses were used to assess the relationship between MRI levels of injury and NLI. RESULTS: All five MRI parameters, namely (1) upper and (2) lower boundaries of cord edema, (3) lesion epicenter, and (4) upper and (5) lower boundaries of cord hemorrhage demonstrated statistically significant, positive correlations with NLI. The MRI locations of upper and lower boundary of hemorrhage were found to have the strongest correlation with NLI (r = 0.72 and 0.61, respectively; p < 0.01). A weaker (low to moderate) correlation existed between lower boundary of cord edema and NLI (r = 0.30; p < 0.01). Upper boundary of cord hemorrhage on MRI demonstrated the best agreement with NLI (mean difference 0.03 ± 0.73; p < 0.01) by Bland-Altman analysis. CONCLUSIONS: MRI level of injury has the potential to serve as a surrogate for NLI in instances where the neurologic examination is either unavailable or unreliable.

Reliability and validity of the capabilities of upper extremity test (CUE-T) in subjects with chronic spinal cord injury.

OBJECTIVE: To determine the reliability and validity of the capabilities of upper extremity test (CUE-T), a measure of functional limitations, in patients with chronic tetraplegia. DESIGN: Repeated measures. SETTING: Outpatient rehabilitation center. PARTICIPANTS: Fifty subjects (36 male/14 female) with spinal cord injury (SCI) of ≥1-year duration participated. Subjects were 17-81 years old (mean 48.1 ± 18.2); neurological levels ranged from C2 through T6, American Spinal Injury Association Impairment Scale grades A-D. INTERVENTIONS: Not applicable. OUTCOME MEASURES: Intraclass correlation coefficients (ICC), weighted kappa and repeatability values for CUE-T; Spearman correlations of CUE-T with upper extremity motor scores (UEMS), and self-care and mobility portions of the Spinal Cord Independence Measure, vIII (SCIM III). RESULTS: Score ranges for UEMS were 8-50, CUE-T 7-135, self-care SCIM 0-20, and mobility SCIM 0-40. The ICC values for total, right, and left side scores were excellent (0.97-0.98; 95% confidence interval 0.96-0.99). Item weighted kappa values were ≥0.60 for all but five items, four of which were right and left pronation and supination. Repeatability of total score was 10.8 points, right and left sides 6.3 and 6.1 points. Spearman correlations of the total CUE-T with the UEMS and SCIM self-care and mobility scores were 0.83, 0.70, and 0.55 respectively. CONCLUSIONS: The CUE-T displays excellent test-retest reliability, and good-excellent correlation with impairment and capacity measures in persons with chronic SCI. After revising pronation and supination test procedures, the sensitivity to change should be determined.

Development and initial evaluation of the SCI-FI/AT.

OBJECTIVES: To describe the domain structure and calibration of the Spinal Cord Injury Functional Index for samples using Assistive Technology (SCI-FI/AT) and report the initial psychometric properties of each domain. DESIGN: Cross sectional survey followed by computerized adaptive test (CAT) simulations. SETTING: Inpatient and community settings. PARTICIPANTS: A sample of 460 adults with traumatic spinal cord injury (SCI) stratified by level of injury, completeness of injury, and time since injury. INTERVENTIONS: None MAIN OUTCOME MEASURE: SCI-FI/AT RESULTS: Confirmatory factor analysis (CFA) and Item response theory (IRT) analyses identified 4 unidimensional SCI-FI/AT domains: Basic Mobility (41 items) Self-care (71 items), Fine Motor Function (35 items), and Ambulation (29 items). High correlations of full item banks with 10-item simulated CATs indicated high accuracy of each CAT in estimating a person's function, and there was high measurement reliability for the simulated CAT scales compared with the full item bank. SCI-FI/AT item difficulties in the domains of Self-care, Fine Motor Function, and Ambulation were less difficult than the same items in the original SCI-FI item banks. CONCLUSION: With the development of the SCI-FI/AT, clinicians and investigators have available multidimensional assessment scales that evaluate function for users of AT to complement the scales available in the original SCI-FI.

mHealth-Based Just-in-Time Adaptive Intervention to Improve the Physical Activity Levels of Individuals With Spinal Cord Injury: Protocol for a Randomized Controlled Trial.

BACKGROUND: The lack of regular physical activity (PA) in individuals with spinal cord injury (SCI) in the United States is an ongoing health crisis. Regular PA and exercise-based interventions have been linked with improved outcomes and healthier lifestyles among those with SCI. Providing people with an accurate estimate of their everyday PA level can promote PA. Furthermore, PA tracking can be combined with mobile health technology such as smartphones and smartwatches to provide a just-in-time adaptive intervention (JITAI) for individuals with SCI as they go about everyday life. A JITAI can prompt an individual to set a PA goal or provide feedback about their PA levels. OBJECTIVE: The primary aim of this study is to investigate whether minutes of moderate-intensity PA among individuals with SCI can be increased by integrating a JITAI with a web-based PA intervention (WI) program. The WI program is a 14-week web-based PA program widely recommended for individuals with disabilities. A secondary aim is to investigate the benefit of a JITAI on proximal PA, defined as minutes of moderate-intensity PA within 120 minutes of a PA feedback prompt. METHODS: Individuals with SCI (N=196) will be randomized to a WI arm or a WI+JITAI arm. Within the WI+JITAI arm, a microrandomized trial will be used to randomize participants several times a day to different tailored feedback and PA recommendations. Participants will take part in the 24-week study from their home environment in the community. The study has three phases: (1) baseline, (2) WI program with or without JITAI, and (3) PA sustainability. Participants will provide survey-based information at the initial meeting and at the end of weeks 2, 8, 16, and 24. Participants will be asked to wear a smartwatch every day for ≥12 hours for the duration of the study. RESULTS: Recruitment and enrollment began in May 2023. Data analysis is expected to be completed within 6 months of finishing participant data collection. CONCLUSIONS: The JITAI has the potential to achieve long-term PA performance by delivering tailored, just-in-time feedback based on the person's actual PA behavior rather than a generic PA recommendation. New insights from this study may guide intervention designers to develop engaging PA interventions for individuals with disability. TRIAL REGISTRATION: ClinicalTrials.gov NCT05317832; https://clinicaltrials.gov/study/NCT05317832. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57699.

Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: a safety and efficacy trial.

Cervical spinal cord injury (SCI) leads to permanent impairment of arm and hand functions. Here we conducted a prospective, single-arm, multicenter, open-label, non-significant risk trial that evaluated the safety and efficacy of ARCEX Therapy to improve arm and hand functions in people with chronic SCI. ARCEX Therapy involves the delivery of externally applied electrical stimulation over the cervical spinal cord during structured rehabilitation. The primary endpoints were safety and efficacy as measured by whether the majority of participants exhibited significant improvement in both strength and functional performance in response to ARCEX Therapy compared to the end of an equivalent period of rehabilitation alone. Sixty participants completed the protocol. No serious adverse events related to ARCEX Therapy were reported, and the primary effectiveness endpoint was met. Seventy-two percent of participants demonstrated improvements greater than the minimally important difference criteria for both strength and functional domains. Secondary endpoint analysis revealed significant improvements in fingertip pinch force, hand prehension and strength, upper extremity motor and sensory abilities and self-reported increases in quality of life. These results demonstrate the safety and efficacy of ARCEX Therapy to improve hand and arm functions in people living with cervical SCI. ClinicalTrials.gov identifier: NCT04697472 .

Assessing functional recovery for individuals with spinal cord injury post-discharge from inpatient rehabilitation.

OBJECTIVE: To determine the associations between trauma variables, acute phase-related variables, and patient-level characteristics with functional recovery during the first-year post-discharge from inpatient rehabilitation facilities (IRF) for individuals with spinal cord injury (SCI). DESIGN: Retrospective cohort analysis. SETTING: Two SCI Model Centers in Pennsylvania, United States. METHODS: We were able to link 378 individuals with traumatic SCI between the Pennsylvania Trauma Systems Outcomes Study and the National SCI Model Systems databases. Nineteen individuals with SCI were excluded due to missing data. We estimated functional recovery based on changes in functional independence measure (FIM) total motor score during the first-year post-discharge from IRF in 359 individuals with SCI, who did not have any missing data, using ordinary least squares regression (OLS). RESULTS: After discharge from IRF the majority of individuals with SCI improved over the first-year post-injury. Individuals with cervical A-C (injury severity group) who were older had a slight decrease in motor FIM at 1-year post-injury. Regression analysis indicated that lower functional recovery was associated with being of Black and Hispanic race and ethnicity, higher injury severity group, occurrence of non-pulmonary infection during acute care, and longer length of stay at IRF (R2 = 0.36). CONCLUSIONS: Patient-level characteristics, trauma variables, and acute phase-related variables were associated with functional recovery post-discharge from IRF. Further research is necessary to collect and assess post-rehabilitation and socio-economic factors that play a critical role in continued functional recovery in the community.

Soluble Nogo-Receptor-Fc decoy (AXER-204) in patients with chronic cervical spinal cord injury in the USA: a first-in-human and randomised clinical trial.

BACKGROUND: Spinal cord injury (SCI) causes neural disconnection and persistent neurological deficits, so axon sprouting and plasticity might promote recovery. Soluble Nogo-Receptor-Fc decoy (AXER-204) blocks inhibitors of axon growth and promotes recovery of motor function after SCI in animals. This first-in-human and randomised trial sought to determine primarily the safety and pharmacokinetics of AXER-204 in individuals with chronic SCI, and secondarily its effect on recovery. METHODS: We conducted a two-part study in adults (aged 18-65 years) with chronic (>1 year) cervical traumatic SCI at six rehabilitation centres in the USA. In part 1, AXER-204 was delivered open label as single intrathecal doses of 3 mg, 30 mg, 90 mg, or 200 mg, with primary outcomes of safety and pharmacokinetics. Part 2 was a randomised, parallel, double-blind comparison of six intrathecal doses of 200 mg AXER-204 over 104 days versus placebo. Participants were randomly allocated (1:1) by investigators using a central electronic system, stratified in blocks of four by American Spinal Injury Association Impairment Scale grade and receipt of AXER-204 in part 1. All investigators and patients were masked to treatment allocation until at least day 169. The part 2 primary objectives were safety and pharmacokinetics, with a key secondary objective to assess change in International Standards for Neurological Classification of SCI (ISNCSCI) Upper Extremity Motor Score (UEMS) at day 169 for all enrolled participants. This trial is registered with ClinicalTrials.gov, NCT03989440, and is completed. FINDINGS: We treated 24 participants in part 1 (six per dose; 18 men, six women), and 27 participants in part 2 (13 placebo, 14 AXER-204; 23 men, four women), between June 20, 2019, and June 21, 2022. There were no deaths and no discontinuations from the study due to an adverse event in part 1 and 2. In part 2, treatment-related adverse events were of similar incidence in AXER-204 and placebo groups (ten [71%] vs nine [69%]). Headache was the most common treatment-related adverse event (five [21%] in part 1, 11 [41%] in part 2). In part 1, AXER-204 reached mean maximal CSF concentration 1 day after dosing with 200 mg of 412 000 ng/mL (SD 129 000), exceeding those concentrations that were efficacious in animal studies. In part 2, mean changes from baseline to day 169 in ISNCSCI UEMS were 1·5 (SD 3·3) for AXER-204 and 0·9 (2·3) for placebo (mean difference 0·54, 95% CI -1·48 to 2·55; p=0·59). INTERPRETATION: This study delivers the first, to our knowledge, clinical trial of a rationally designed pharmacological treatment intended to promote neural repair in chronic SCI. AXER-204 appeared safe and reached target CSF concentrations; exploratory biomarker results were consistent with target engagement and synaptic stabilisation. Post-hoc subgroup analyses suggest that future trials could investigate efficacy in patients with moderately severe SCI without prior AXER-204 exposure. FUNDING: Wings for Life Foundation, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences, National Institute on Drug Abuse, and ReNetX Bio.